[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia]. / Verbesserung der koronaren Vasodilatationskapazität durch medikamentöse Lipidsenkung bei Patienten im Frühstadium der koronaren Atherosklerose mit eingeschränkter Koronarreserve und mässiggradiger LDL-Hypercholesterinämie.

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

Improvement of coronary vasodilatation capacity through single LDL apheresis.

A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.